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Matrine Impairs Platelet Function and Thrombosis and Inhibits ROS Production

Matrine is a naturally occurring alkaloid and possesses a wide range of pharmacological properties, such as anti-cancer, anti-oxidant, anti-inflammatory effects. However, whether it affects platelet function and thrombosis remains unclear. This study aims to evaluate the effect of matrine on platele...

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Autores principales: Zhang, Sixuan, Gui, Xiang, Ding, Yangyang, Tong, Huan, Ju, Wen, Li, Yue, Li, Zhenyu, Zeng, Lingyu, Xu, Kailin, Qiao, Jianlin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339414/
https://www.ncbi.nlm.nih.gov/pubmed/34366869
http://dx.doi.org/10.3389/fphar.2021.717725
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author Zhang, Sixuan
Gui, Xiang
Ding, Yangyang
Tong, Huan
Ju, Wen
Li, Yue
Li, Zhenyu
Zeng, Lingyu
Xu, Kailin
Qiao, Jianlin
author_facet Zhang, Sixuan
Gui, Xiang
Ding, Yangyang
Tong, Huan
Ju, Wen
Li, Yue
Li, Zhenyu
Zeng, Lingyu
Xu, Kailin
Qiao, Jianlin
author_sort Zhang, Sixuan
collection PubMed
description Matrine is a naturally occurring alkaloid and possesses a wide range of pharmacological properties, such as anti-cancer, anti-oxidant, anti-inflammatory effects. However, whether it affects platelet function and thrombosis remains unclear. This study aims to evaluate the effect of matrine on platelet function and thrombus formation. Human platelets were treated with matrine (0–1 mg/ml) for 1 h at 37°C followed by measuring platelet aggregation, granule secretion, receptor expression by flow cytometry, spreading and clot retraction. In addition, matrine (10 mg/kg) was injected intraperitoneally into mice to measure tail bleeding time, arterial and venous thrombus formation. Matrine dose-dependently inhibited platelet aggregation and ATP release in response to either collagen-related peptide (Collagen-related peptide, 0.1 μg/ml) or thrombin (0.04 U/mL) stimulation without altering the expression of P-selectin, glycoprotein Ibα, GPVI, or αIIbβ3. In addition, matrine-treated platelets presented significantly decreased spreading on fibrinogen or collagen and clot retraction along with reduced phosphorylation of c-Src. Moreover, matrine administration significantly impaired the in vivo hemostatic function of platelets, arterial and venous thrombus formation. Furthermore, in platelets stimulated with CRP or thrombin, matrine significantly reduced Reactive oxygen species generation, inhibited the phosphorylation level of ERK1/2 (Thr202/Tyr204), p38 (Thr180/Tyr182) and AKT (Thr308/Ser473) as well as increased VASP phosphorylation (Ser239) and intracellular cGMP level. In conclusion, matrine inhibits platelet function, arterial and venous thrombosis, possibly involving inhibition of ROS generation, suggesting that matrine might be used as an antiplatelet agent for treating thrombotic or cardiovascular diseases.
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spelling pubmed-83394142021-08-06 Matrine Impairs Platelet Function and Thrombosis and Inhibits ROS Production Zhang, Sixuan Gui, Xiang Ding, Yangyang Tong, Huan Ju, Wen Li, Yue Li, Zhenyu Zeng, Lingyu Xu, Kailin Qiao, Jianlin Front Pharmacol Pharmacology Matrine is a naturally occurring alkaloid and possesses a wide range of pharmacological properties, such as anti-cancer, anti-oxidant, anti-inflammatory effects. However, whether it affects platelet function and thrombosis remains unclear. This study aims to evaluate the effect of matrine on platelet function and thrombus formation. Human platelets were treated with matrine (0–1 mg/ml) for 1 h at 37°C followed by measuring platelet aggregation, granule secretion, receptor expression by flow cytometry, spreading and clot retraction. In addition, matrine (10 mg/kg) was injected intraperitoneally into mice to measure tail bleeding time, arterial and venous thrombus formation. Matrine dose-dependently inhibited platelet aggregation and ATP release in response to either collagen-related peptide (Collagen-related peptide, 0.1 μg/ml) or thrombin (0.04 U/mL) stimulation without altering the expression of P-selectin, glycoprotein Ibα, GPVI, or αIIbβ3. In addition, matrine-treated platelets presented significantly decreased spreading on fibrinogen or collagen and clot retraction along with reduced phosphorylation of c-Src. Moreover, matrine administration significantly impaired the in vivo hemostatic function of platelets, arterial and venous thrombus formation. Furthermore, in platelets stimulated with CRP or thrombin, matrine significantly reduced Reactive oxygen species generation, inhibited the phosphorylation level of ERK1/2 (Thr202/Tyr204), p38 (Thr180/Tyr182) and AKT (Thr308/Ser473) as well as increased VASP phosphorylation (Ser239) and intracellular cGMP level. In conclusion, matrine inhibits platelet function, arterial and venous thrombosis, possibly involving inhibition of ROS generation, suggesting that matrine might be used as an antiplatelet agent for treating thrombotic or cardiovascular diseases. Frontiers Media S.A. 2021-07-22 /pmc/articles/PMC8339414/ /pubmed/34366869 http://dx.doi.org/10.3389/fphar.2021.717725 Text en Copyright © 2021 Zhang, Gui, Ding, Tong, Ju, Li, Li, Zeng, Xu and Qiao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhang, Sixuan
Gui, Xiang
Ding, Yangyang
Tong, Huan
Ju, Wen
Li, Yue
Li, Zhenyu
Zeng, Lingyu
Xu, Kailin
Qiao, Jianlin
Matrine Impairs Platelet Function and Thrombosis and Inhibits ROS Production
title Matrine Impairs Platelet Function and Thrombosis and Inhibits ROS Production
title_full Matrine Impairs Platelet Function and Thrombosis and Inhibits ROS Production
title_fullStr Matrine Impairs Platelet Function and Thrombosis and Inhibits ROS Production
title_full_unstemmed Matrine Impairs Platelet Function and Thrombosis and Inhibits ROS Production
title_short Matrine Impairs Platelet Function and Thrombosis and Inhibits ROS Production
title_sort matrine impairs platelet function and thrombosis and inhibits ros production
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339414/
https://www.ncbi.nlm.nih.gov/pubmed/34366869
http://dx.doi.org/10.3389/fphar.2021.717725
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